Differential effects of painful and non-painful stimulation on tactile processing in fibromyalgia syndrome and subjects with masochistic behaviour

Background

In healthy subjects repeated tactile stimulation in a conditioning test stimulation paradigm yields attenuation of primary (S1) and secondary (S2) somatosensory cortical activation, whereas a preceding painful stimulus results in facilitation.

Methodology/Principal Findings

Since previous data suggest that cognitive processes might affect somatosensory processing in S1, the present study aims at investigating to what extent cortical reactivity is altered by the subjective estimation of pain. To this end, the effect of painful and tactile stimulation on processing of subsequently applied tactile stimuli was investigated in patients with fibromyalgia syndrome (FMS) and in subjects with masochistic behaviour (MB) by means of a 122-channel whole-head magnetoencephalography (MEG) system. Ten patients fulfilling the criteria for the diagnosis of FMS, 10 subjects with MB and 20 control subjects matched with respect to age, gender and handedness participated in the present study. Tactile or brief painful cutaneous laser stimuli were applied as conditioning stimulus (CS) followed by a tactile test stimulus (TS) 500 ms later. While in FMS patients significant attenuation following conditioning tactile stimulation was evident, no facilitation following painful stimulation was found. By contrast, in subjects with MB no attenuation but significant facilitation occurred. Attenuation as well as facilitation applied to cortical responses occurring at about 70 ms but not to early S1 or S2 responses. Additionally, in FMS patients the amount of attenuation was inversely correlated with catastrophizing tendency.

Conclusion

The present results imply altered cortical reactivity of the primary somatosensory cortex in FMS patients and MB possibly reflecting differences of individual pain experience.     

Effects of betaine and condensed molasses solubles on nitrogen balance and nutrient digestibility in piglets fed diets deficient in methionine and low in compatible osmolytes

A balance experiment was carried out to investigate the effects of betaine monohydrate (BET) or betaine derived from condensed molasses solubles (CMS) as a substitute for methionine and choline on nitrogen (N) balance and total tract nutrient digestibility in weaned piglets. The experiment included four treatments with 32 barrows with an average initial body weight (BW) of 13.5 kg. The supplementation of DL-methionine and choline (positive control = PC) to the basal diet, which was deficient in methionine and low in compatible osmolytes in the form of betaine or its precursor choline (negative control = NC) resulted in a significant increase in N retention of 0.8 g/d. The substitution of DL-methionine and choline with BET or CMS did not affect N retention compared to the PC and the NC treatment either. Feeding the PC diet increased the digestibilities of organic matter, NDF, ADF, NFE, crude ash, Ca, P, methionine, tryptophan and cystine by 1.9%, 7.3%, 9.7%, 1.1%, 6.3%, 13.9%, 7.7%, 15.9%, 4.3% and 2.8%, respectively, and tended (p < 0.20) to increase the digestibilities of most other amino acids by 1.6-3.4%. Digestibility of CP, EE (HCl), Mg and Na was 3.1% (p=0.09), 5.1% (p=0.09), 5.1% (p= 0.06) and 3.3% (p= 0.17) higher, respectively, when compared to the NC treatment. BET and CMS supplementation increased most nutrient digestibilities in the same magnitude as for the PC treatment. In summary, the supplementation of betaine, originating from different sources, to a diet with low contents of compatible osmolytes increased in particular the fermentation of fibre and enhanced mineral absorption. The supplementation of the NC with DL-methionine was more efficient in improving N retention than the replacement of DL-methionine by betaine originating from BET or CMS.     

Mapping determinants of gene expression plasticity by genetical genomics in C. elegans

Recent genetical genomics studies have provided intimate views on gene regulatory networks. Gene expression variations between genetically different individuals have been mapped to the causal regulatory regions, termed expression quantitative trait loci. Whether the environment-induced plastic response of gene expression also shows heritable difference has not yet been studied. Here we show that differential expression induced by temperatures of 16 °C and 24 °C has a strong genetic component in Caenorhabditis elegans recombinant inbred strains derived from a cross between strains CB4856 (Hawaii) and N2 (Bristol). No less than 59% of 308 trans-acting genes showed a significant eQTL-by-environment interaction, here termed plasticity quantitative trait loci. In contrast, only 8% of an estimated 188 cis-acting genes showed such interaction. This indicates that heritable differences in plastic responses of gene expression are largely regulated in trans. This regulation is spread over many different regulators. However, for one group of trans-genes we found prominent evidence for a common master regulator: a transband of 66 coregulated genes appeared at 24 °C. Our results suggest widespread genetic variation of differential expression responses to environmental impacts and demonstrate the potential of genetical genomics for mapping the molecular determinants of phenotypic plasticity.     

Ab initio prediction of metabolic networks using Fourier transform mass spectrometry data

Fourier transform mass spectrometry has recently been introduced into the field of metabolomics as a technique that enables the mass separation of complex mixtures at very high resolution and with ultra high mass accuracy. Here we show that this enhanced mass accuracy can be exploited to predict large metabolic networks ab initio, based only on the observed metabolites without recourse to predictions based on the literature. The resulting networks are highly information-rich and clearly non-random. They can be used to infer the chemical identity of metabolites and to obtain a global picture of the structure of cellular metabolic networks. This represents the first reconstruction of metabolic networks based on unbiased metabolomic data and offers a breakthrough in the systems-wide analysis of cellular metabolism.     

Chemical carcinogens in non-enzymatic cytosine deamination: 3-isocyanatoacrylonitrile

Uracil has long been known as the main product of nitrosative cytosine deamination in aqueous solution. Recent mechanistic studies of cytosinediazonium ion suggest that the cation formed by its dediazoniation can ring-open to N-protonated (Z,s-cis)-3-isocyanatoacrylonitrile 7. Stereochemical preferences are discussed of the 3-isocyanatoacrylonitriles (Z,s-cis)-10, (E,s-cis)-11, (Z,s-trans)-12, and (E,s-trans)-13. The electronic structures of 7 and 10–13 have been analyzed and a rationale is provided for the thermodynamic preference for (Z,s-cis)-10. It is shown that s-cis/s-trans-interconversion occurs via C−N rotation–inversion paths with barriers below 3 kcal mol⁻¹. The proton affinities of 3-isocyanatoacrylonitrile 10 and water are nearly identical and, thus, 3-isocyanatoacrylonitriles can and should be formed in aqueous media from 7 along with 3-aminoacrylonitriles 9. The results highlight the relevance of the chemistry of 3-isocyanatoacrylonitriles for the understanding of the chemical toxicology of nitrosation of the nucleobase cytosine. Electronic Supplementary Material Supplementary Material is available for this article at Dedicated to professor Dr. Paul von Ragué Schleyer on the occasion of his 75th birthday     

Methylation is the initial reaction in anaerobic naphthalene degradation by a sulfate-reducing enrichment culture

The sulfate-reducing culture N47 can utilize naphthalene or 2-methylnaphthalene as the sole carbon source and electron donor. Here we show that the initial reaction in the naphthalene degradation pathway is a methylation to 2-methylnaphthalene which then undergoes the subsequent oxidation to the central metabolite 2-naphthoic acid, ring reduction and cleavage. Specific metabolites occurring exclusively during anaerobic degradation of 2-methylnaphthalene were detected during growth on naphthalene, i.e. naphthyl-2-methyl-succinate and naphthyl-2-methylene-succinate. Additionally, all three enzymes involved in anaerobic degradation of 2-methylnaphthalene to 2-naphthoic acid that could be measured in vitro so far, i.e. naphthyl-2-methyl-succinate synthase, succinyl-CoA:naphthyl-2-methyl-succinate CoA-transferase and naphthyl-2-methyl-succinyl-CoA dehydrogenase were also detected in naphthalene-grown cells with similar activities. Induction experiments were performed to study the growth behaviour of the cell when transferred from naphthalene to 2-methylnaphthalene or vice versa. When the cells were transferred from naphthalene to 2-methylnaphthalene they grew immediately, indicating that no new enzymes had to be induced. On the contrary, the transfer of cells from 2-methylnaphthalene to naphthalene caused a lag-phase of almost 100 days demonstrating that an additional catabolic enzyme has to be activated in this case. We propose the methylation as a novel general mechanism of activation reactions in anaerobic degradation of unsubstituted aromatic hydrocarbons.     

Score-based prediction of genomic islands in prokaryotic genomes using hidden Markov models

Background  

Horizontal gene transfer (HGT) is considered a strong evolutionary force shaping the content of microbial genomes in a substantial manner. It is the difference in speed enabling the rapid adaptation to changing environmental demands that distinguishes HGT from gene genesis, duplications or mutations. For a precise characterization, algorithms are needed that identify transfer events with high reliability. Frequently, the transferred pieces of DNA have a considerable length, comprise several genes and are called genomic islands (GIs) or more specifically pathogenicity or symbiotic islands.